Nickel metalloenzymes

Like most trace elements, nickel can activate various enzymes in vitro, but no enzyme has been shown to require nickel, specifically, to be activated. Howevei, mease has been shown to be a nickel metalloenzyme and has been found to contain 6 to 8 atoms of nickel per mole of enzyme (Fishbein et al.. 1976). RNA (ribonucleic add) preparations from diverse sources consistently contain nickel in concentrations many times higher than those found in native materials from which the RNA ts isolated (Wacker-Vallee, 1959 Sunderman, 1965). Nickel may serve to stabilize the ordered structure of RNA. Nickel may have a role in maintaining ribosomal structure (Tal, 1968, 1969). These studies and other information have led to the suggestion that nickel may play a role in nucleic acid and/or protein metabolism. 

Roughly 30% of enzymes are metalloenzymes or require metal ions for activity and the present chapter will concentrate on the chemisty and structure of the plant metalloenzymes. As analytical methods have improved it has been possible to establish a metal ion requirement for a variety of enzymes which were initially considered to be pure proteins. A dramatic example is provided by the enzyme urease isolated from Jack beans and first crystallised by Sumner (1926) (the first enzyme to be crystallised). Sumner defined an enzyme as a pure protein with catalytic activity, however, Zerner and his coworkers (Dixon et al., 1975) established that urease is in fact a nickel metalloenzyme. Jack bean urease contains two moles of nickel(II) per mole of active sites and at least one of these metal ions is implicated in its mechanism of action. 

Since 1975 four classes of nickel metalloenzymes have been identified (77). The nickel hydrogenases and carbon monoxide dehydrogenases are considered here and the dinuclear active site of urease is described in Section IVB. The fourth class, methyl-S-coenzyme-M reductases,... 

Urease, the first nickel metalloenzyme to be discovered 108), catalyzes the hydrolysis of urea in bacteria, plants, and some invertebrates 71, 109) ... 

Anke et al. 1980a, Spears and Hatfield 1978). Urease was the first natural nickel metalloenzyme discovered by Fishbein et al. (1976). Urease is a component of several leguminous plants (jack bean), and is synthesized by the rumen bacteria. Urease catalyzes the reaction ... 

Can M, Armstrong FA, Ragsdale SW (2014) Structure, function, and mechanism of the nickel metalloenzymes, CO dehydrogenase, and acetyl-CoA synthase. Chem Rev 114 4149 174. doi 10.1021/cr400461p... 

The most important degradative method for the determination of urea in the natural water samples is based on its conversion to carbon dioxide and ammonia by hydrolysis obtained with a nickel metalloenzyme (urease). In the manual procedure outlined by McCarthy [89] for the analysis in seawater, the enzymatic hydrolysis of urea was carried out at 50°C for 20 min, in the range of pH from 6.4 to 8.0, using a solution of crude lyophilized jack beam urease. After the samples were cooled at room temperature, NH4 concentration was determined by manual colorimetric method after cooling the samples at room temperature. The ambient concentration of NH4 and the analytical blank (NH4 contained in the reagents and in the urease solution) have to be subtracted for any sample to obtain the concentration of urea. In this reference study, the precision (RSD) was 1% at the concentration of urea equal to 1 pmol N A manual indirect methodology was also described by Katz and Rechnitz [209] and the method was revised in other following studies [9,53,197,198]. It persists with minor modifications in recent works on the field and in culture experiments [71,199-202] and for determination of isotope ratio in urea by elemental... 

Nickel is required by plants when urea is the source of nitrogen (Price and Morel, 1991). Bicarbonate uptake by cells may be limited by Zn as HCOT transport involves the zinc metal-loenzyme carbonic anhydrase (Morel et al., 1994). Cadmium is not known to be required by organisms but because it can substitute for Zn in some metalloenzymes it can promote the growth of Zn-limited phytoplankton (Price and Morel, 1990). Cobalt can also substitute for Zn but less efficiently than Cd. 

This short section attempts to bring together the range of metalloenzymes that are encountered in biodegradation and biotransformation. Fe is the most common component of enzymes, and is followed in freqnency by zinc and molybdennm, while some important enzymes contain nickel, copper, manganese, tnngsten, or vanadinm. 

Kinetic evidence obtained for intramolecular proton transfer between nickel and coordinated thiolate, in a tetrahedral complex containing the bulky triphos ligand (Pl PCE CE PPh to prevent interference from binuclear p-thiolate species, is important with respect to the mechanisms of action of a number of metalloenzymes, of nickel (cf. urease, Section VII. B.4) and of other metals (289). 

Researchers studying the metalloenzyme hydrogenase would like to design small compounds that mimic this enzyme s ability to reversibly reduce protons to H2 and H2 to 2H+, using an active center that contains iron and nickel. Cobalamins (vitamin and its derivatives) contain an easily activated Co-C bond that has a number of biological functions, one of which is as a methyl transferase, 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). This enzyme converts homocysteine (an amino acid that has one more CH2 group in its alkyl side chain than cysteine see Figure 2.2) to methionine as methylcobalamin is converted to cobalamin. 

In zinc metalloenzymes. zinc is a selective stoichiometric constituent and is essential for catalytic activity. It is frequently present in numerical correspondence with the number of active enzymatic sites, coenzyme binding sites, or enzyme subunits Removal of zinc results in loss of activity. Inhibition by metal complexing agents is a characteristic feature of zinc metalloenzymes. However, no direct relationship holds between the inhibitory effectiveness of these agents and their affinity for ionic zinc. Although zinc is the only constituent of zinc metalloenzymes in vivo, it can be replaced by other metals m vitro, such as cobalt, nickel, iron, manganese, cadmium, mercury, and lead, as m the case of carboxy-peprida.ses. 

Nickel, atomic number 28, is a transition metal with a variety of essential uses in alloys, catalysts, and other applications. It is strongly suspected of being an essential trace element for human nutrition, although definitive evidence has not yet established its essentiality to humans. A nickel-containing urease metalloenzyme has been found in the jack bean. 

Nickel(I) complexes of N4 macrocycles can be prepared by reduction of the corresponding Ni11 complexes with sodium amalgam. They possess more or less distorted square-planar structures.19 By contrast, the one-electron reduction of Ni porphyrin complexes may result in Ni1 porphyrins or Nin jr-anion radicals, depending on the reaction conditions.20 Complexes of this kind are useful models for the Ni sites in certain metalloenzymes (see below). 

Active Sites, Copper Proteins Oxidases, Copper Proteins with Type 1 Sites, Copper Proteins with Type 2 Sites, Copper Enzymes in Denitrification, Iron-Sulfur Models of Protein Active Sites, Iron-Sulfur Proteins Nickel Enzymes Cofactors and Nickel Models of Protein Active Sites). However, since many metalloenzymes have been found or postulated to incorporate metal-sulfur bonding, it is appropriate that a very short sununary be included here. 

The enzyme urease catalyzes the hydrolysis of urea to form carbamate ion (equation 32). At pH 7.0 and 38 °C, the urease-catalyzed hydrolysis of urea is at least 10 " times as fast as the spontaneous hydrolysis of urea. Jack bean urease is a nickel(II) metalloenzyme with each of its six identical subunits containing one active site and two metal ions, and at least one of these nickel ions is implicated in the hydrolysis. It has been suggested that all substrates for urease (urea, N-hydroxyurea, 7V-methylurea, semicarbazide formamide and acetamide) are activated towards nucleophilic attack on carbon as a result of O-coordination to the active nickel(II) site as in (155). Nickel(II) ions have been found to promote the ethanolysis and hydrolysis of JV-(2-pyridylmethyl)urea (Scheme 39) and this system is considered to be a useful model for the enzyme. 

A wide range of metal ions is present in metalloenzymes as cofactors. Copper zinc snperoxide dismntase is a metalloenzyme that nses copper and zinc to help catalyze the conversion of snperoxide anion to molecnlar oxygen and hydrogen peroxide. Thermolysin is a protease that nses a tightly bonnd zinc ion to activate a water atom, which then attacks a peptide bond. Aconitase is one of the enzymes of the citric acid cycle it contains several iron atoms bonnd in the form of iron-sulfur clusters, which participate directly in the isomerization of citrate to isocitrate. Other metal ions fonnd as cofactors in metalloenzymes include molybdenum (in nitrate rednctase), seleninm (in glutathione peroxidase), nickel (in urease), and vanadinm (in fungal chloroperoxidase). see also Catalysis and Catalysts Coenzymes Denaturation Enzymes Krebs Cycle. 

In order to carry out most biochemical reactions, metalloenzymes generally utilize the rarer transition metal ions. Elements such as zinc, copper, iron, nickel, and cobalt are found in low concentrations in plasma and seawater and yet the enzyme has to select the appropriate metal ion from them. There is evidence for the existence of proteins that can chaperone specific metal ions to their appropriate sites in apoenzymes, protecting the metal ions from adverse reactions as they are guided to their required location [5]. How does the enzyme attempt to select out the one metal ion it requires The answer is that the chemistry of the metal ion is used as a basis for selection. Each metal ion has some property that is different from that of most others, but, in fact, there is often considerable overlap in these properties so that a given enzyme may bind one of several different cations in one specific site. Some relevant data are provided in Tables 1 and 2. The metalloenzyme contains within its overall design an arrangement of preferred side-chain functional groups with the correct size hole to bind the required metal ions in an appropriate hydrophobic or hydrophilic environment. Thus the metalloenzyme binds metal ions... 

Dixon NE, Gazzola C, Blakeley RL and Zerner B (1975) Jack bean urease a metalloenzyme A simple biological role for nickel J Am Chem Soc 97 4131-4133. 

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